Chronic Obstructive Pulmonary Disease (COPD)
COPD is the third leading cause of death worldwide — and one of the most commonly misdiagnosed conditions in general medicine. This guide walks the whole disease: what it is, why it happens, how the lung is actually destroyed, how to prove it with spirometry, and how to treat it at every step.
01What COPD is
"COPD is a heterogeneous lung condition characterised by chronic respiratory symptoms (dyspnoea, cough, sputum production, exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction."
— Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024 ReportStrip that down and three ideas matter. First, airflow obstruction — air leaves the lung too slowly. Second, that obstruction is persistent: it does not fully reverse with a bronchodilator, which is what separates COPD from asthma. Third, it is heterogeneous — two patients with the same FEV₁ can have entirely different diseases, one dominated by airway inflammation and the other by alveolar destruction.
The functional definition every clinician must memorise is a single number: a post-bronchodilator FEV₁/FVC ratio below 0.70. Without spirometry demonstrating that, you do not have a diagnosis of COPD — you have a suspicion. This matters enormously in practice, because roughly a third of patients labelled "COPD" on clinical grounds alone turn out, on testing, not to have airflow obstruction at all.
Older texts split COPD into "emphysema" and "chronic bronchitis" as if they were two diseases. They are not. They are two pathological patterns that coexist in most real patients in varying proportion. Modern practice diagnoses COPD physiologically and then describes the dominant phenotype — which is what actually changes your drug choice.
02Etiology & risk factors
COPD is the product of a lifetime of interaction between inhaled toxins and host susceptibility. Think of it as cumulative insult against individual defence. Smoking is the dominant cause in high-income settings, but globally, household air pollution from biomass cooking fuel rivals it — which is why COPD is common in women who have never smoked a cigarette.
Environmental and exposure factors
| Exposure | Mechanism / notes | Relative weight |
|---|---|---|
| Tobacco smoking | The dominant cause. Risk scales with pack-years; roughly 20–30% of persistent smokers develop clinically significant COPD | Very high |
| Biomass fuel smoke | Wood, charcoal, dung, crop residue burned indoors without a flue. The leading cause in low-income settings and in never-smoking women | Very high |
| Occupational dust & fumes | Silica, coal, cadmium, welding fumes, grain dust, isocyanates. Accounts for ~15% of cases | High |
| Ambient air pollution | Particulate matter (PM2.5) and nitrogen dioxide; contributes to both incidence and exacerbations | Moderate |
| Second-hand smoke | Passive exposure, including significant in utero exposure | Moderate |
| Cannabis / waterpipe smoking | Often overlooked in history-taking; contributes independently | Low–moderate |
Host factors
| Host factor | Why it matters |
|---|---|
| Alpha-1 antitrypsin deficiency | The one classic genetic cause. Suspect it in COPD under 45, in a non-smoker, with basal/lower-zone emphysema, or with unexplained liver disease. Test every young COPD patient once. |
| Impaired lung growth | Prematurity, low birth weight, childhood pneumonia and severe childhood asthma reduce peak FEV₁. A lung that never reached full size reaches the obstruction threshold sooner even with normal age-related decline |
| Airway hyper-responsiveness | Independently accelerates FEV₁ decline in smokers |
| Age & sex | Prevalence rises with age. Women appear more susceptible per pack-year smoked |
| Pulmonary tuberculosis | Post-TB structural lung damage is a major and under-recognised cause of fixed obstruction, especially across Africa and Asia |
| HIV infection | Associated with accelerated emphysema, independent of smoking |
| Socioeconomic deprivation | A consistent, strong association — mediated by exposure, nutrition, infection burden and healthcare access |
"Non-smoker" does not exclude COPD. Roughly 25–45% of COPD worldwide occurs in people who never smoked tobacco. If you reflexively drop COPD from the differential the moment a patient denies smoking, you will miss biomass-fuel COPD, post-TB obstruction and alpha-1 antitrypsin deficiency. Always ask what they cook with, and what they breathe at work.
03Types & classification
COPD is classified three different ways, and students routinely conflate them. Keep them separate: pathological pattern (what the tissue looks like), severity of obstruction (what spirometry says), and symptom/exacerbation group (what actually decides treatment).
3.1 By pathological pattern
| Feature | Emphysema-dominant "pink puffer" | Chronic bronchitis-dominant "blue bloater" |
|---|---|---|
| Primary lesion | Alveolar wall destruction | Airway mucus hypersecretion and inflammation |
| Definition basis | Anatomical / pathological | Clinical (cough ≥3 months × 2 years) |
| Build | Thin, cachectic, barrel chest | Overweight, oedematous |
| Dyspnoea | Severe, early | Milder, later |
| Cough & sputum | Scanty | Copious, productive |
| DLCO | Reduced (lost surface area) | Normal or near-normal |
| PaCO₂ | Normal or low (they maintain it by working hard) | Raised — hypercapnia |
| Cor pulmonale | Late | Early and prominent |
| Chest X-ray | Hyperinflated, flat diaphragms, hyperlucent | Increased markings, enlarged heart |
3.2 Anatomical subtypes of emphysema
| Subtype | Site | Zone | Classic association |
|---|---|---|---|
| Centrilobular | Respiratory bronchiole (centre of acinus) | Upper lobes | Cigarette smoking — the commonest pattern |
| Panlobular (panacinar) | Entire acinus, uniformly | Lower lobes | Alpha-1 antitrypsin deficiency |
| Paraseptal (paracinar) | Distal acinus, adjacent to pleura and septa | Subpleural, apical | Apical bullae; spontaneous pneumothorax in tall young men |
| Irregular | Haphazard, around scars | Variable | Post-inflammatory scarring, old TB |
Smoking goes to the top; alpha-1 goes to the bottom. Inhaled smoke deposits preferentially in the better-ventilated upper zones, so smoking emphysema is apical. In alpha-1 antitrypsin deficiency the defect is a circulating protein deficiency, so damage follows blood flow — which is greatest at the lung bases. Lower-zone emphysema on CT should make you order an alpha-1 level.
3.3 GOLD severity of airflow obstruction
Once the ratio confirms obstruction, the FEV₁ as a percentage of predicted grades its severity.
| Grade | FEV₁ % predicted | Label | Typical functional state |
|---|---|---|---|
| GOLD 1 | ≥ 80% | Mild | Often asymptomatic or a "smoker's cough" only |
| GOLD 2 | 50–79% | Moderate | Breathless on hurrying or slight hills — usually when they first present |
| GOLD 3 | 30–49% | Severe | Stops for breath after ~100 m on the flat |
| GOLD 4 | < 30% | Very severe | Housebound; breathless dressing. Consider respiratory failure and cor pulmonale |
3.4 GOLD ABE groups — what actually drives treatment
This is the classification that changes prescriptions. It ignores FEV₁ entirely and uses symptom burden (mMRC or CAT) and exacerbation history instead.
| Group | Exacerbations in past year | Symptoms | Initial therapy |
|---|---|---|---|
| A | 0 or 1 (no hospitalisation) | Low: mMRC 0–1, CAT < 10 | A bronchodilator |
| B | 0 or 1 (no hospitalisation) | High: mMRC ≥ 2, CAT ≥ 10 | LABA + LAMA |
| E | ≥ 2, or ≥ 1 needing hospital admission | Any | LABA + LAMA; add ICS if eosinophils ≥ 300 |
04Pathogenesis — how the lung is destroyed
To understand COPD you first need the normal architecture it destroys. Air passes down a branching conducting tree that ends in gas-exchange units. Two things keep the smallest airways open: cartilage in the larger bronchi, and — critically for COPD — the outward elastic pull of surrounding alveolar walls tethering the bronchioles open. Destroy the alveoli and you have destroyed the scaffolding that holds the small airways patent.
The disease proceeds as an amplified, self-sustaining inflammatory response to inhaled toxins. Follow the cascade:
Inhaled toxin injures the epithelium
Cigarette smoke or biomass smoke delivers thousands of oxidant species onto the airway lining. Cilia are paralysed and then lost, disabling mucociliary clearance — so the irritant stays in contact with the epithelium for far longer than it should.
Innate inflammatory cells are recruited
Damaged epithelium releases IL-8, IL-1β, TNF-α and GM-CSF, drawing in neutrophils, macrophages and CD8⁺ cytotoxic T lymphocytes. This CD8-predominant, neutrophilic pattern is the immunological signature that distinguishes COPD from the eosinophilic, CD4/Th2 pattern of asthma.
Proteases are released and overwhelm defences
Neutrophils release neutrophil elastase, and macrophages release matrix metalloproteinases (notably MMP-9 and MMP-12). Normally alpha-1 antitrypsin neutralises elastase. But smoke oxidises and inactivates alpha-1 antitrypsin at the same time as it recruits more neutrophils — a double hit producing protease–antiprotease imbalance.
Alveolar elastin is digested — emphysema
Unopposed elastase digests the elastin of alveolar septa. Walls rupture, adjacent alveoli coalesce into fewer, larger spaces, and two things are lost at once: gas-exchange surface area (causing hypoxaemia and a falling DLCO) and elastic recoil.
Small airways collapse on expiration
This is the mechanical heart of the disease. With alveolar tethering destroyed, bronchioles are no longer held open. During expiration, rising intrathoracic pressure collapses them before the alveoli have emptied — producing air trapping. Expiratory flow limitation, not inspiratory difficulty, is the defect.
Airway remodelling makes it irreversible
In parallel, chronic inflammation drives goblet cell hyperplasia, squamous metaplasia, smooth muscle hypertrophy and peribronchiolar fibrosis. Scar tissue is structural, not spasm — which is precisely why a bronchodilator cannot fully reverse the obstruction.
Hyperinflation loads the respiratory pump
Trapped gas raises resting lung volume. The diaphragm is pushed down and flattened, so it contracts from a mechanically disadvantaged, shortened position and generates less pressure per unit effort. On exertion, expiratory time shortens and trapping worsens — dynamic hyperinflation, the direct cause of exertional breathlessness.
Gas exchange fails and the right heart is loaded
Destroyed capillary beds and V/Q mismatch produce hypoxaemia. Chronic alveolar hypoxia triggers hypoxic pulmonary vasoconstriction and vascular remodelling → pulmonary hypertension → right ventricular strain and ultimately cor pulmonale. As ventilatory load exceeds capacity, CO₂ retention appears.
If you remember nothing else: COPD is expiratory flow limitation caused by loss of elastic recoil plus narrowed, unsupported small airways — so the lung cannot empty, and what cannot empty accumulates as hyperinflation. Nearly every sign, symptom and treatment in this article follows from that sentence.
05Natural history & progression
Lung function follows a predictable arc across life: FEV₁ rises to a peak in the early twenties, plateaus, then declines. In a healthy non-smoker that decline is roughly 25–30 mL per year. In a susceptible smoker it can reach 60–100 mL per year. Symptoms usually appear only once FEV₁ has fallen below about 50% of predicted — meaning the disease has been silently progressing for decades before the patient complains.
Two routes lead to the same endpoint, and this is a genuinely modern insight: a patient may reach obstruction either by accelerated decline from a normal peak, or by normal decline from a reduced peak — the latter caused by prematurity, low birth weight, childhood infection or severe childhood asthma. Not all COPD is a smoking story.
| Phase | What is happening | What the patient notices |
|---|---|---|
| Susceptibility | Exposure accumulating; small airway inflammation begins | Nothing |
| Preclinical | Small airway loss and early emphysema; FEV₁ falling but still "normal range" | Nothing, or a cough dismissed as "smoker's cough" |
| Symptomatic | FEV₁/FVC < 0.70 established; hyperinflation developing | Breathless on hills and stairs — often blamed on age or weight |
| Exacerbating | Recurrent inflammatory flares, each accelerating decline | "Chest infections" two or three times a winter |
| Advanced | Severe hyperinflation, hypoxaemia, pulmonary hypertension | Breathless at rest and while dressing; ankle swelling |
| Respiratory failure | Hypercapnia, cor pulmonale, cachexia | Housebound; dependent on oxygen; repeated admissions |
Every exacerbation causes a permanent step-down in lung function that often never fully recovers. Frequent exacerbators decline faster, lose more muscle, and die sooner. A patient admitted with a severe exacerbation carries roughly a 1 in 4 risk of death within one year. Preventing the next exacerbation is therefore not symptom control — it is survival treatment.
06Clinical features
Symptoms
| Symptom | Character in COPD | What distinguishes it |
|---|---|---|
| Dyspnoea | Progressive, persistent, worse on exertion. The symptom that finally brings them in | Slowly worsening over years, not episodic; does not fully resolve between bad days |
| Chronic cough | Often the first symptom, frequently productive; may be intermittent | Long dismissed by the patient as a normal "smoker's cough" |
| Sputum production | Usually mucoid and worst in the morning | A change to purulent suggests exacerbation |
| Wheeze & chest tightness | Variable day to day and within a day | Overlaps heavily with asthma — cannot distinguish on its own |
Grading breathlessness — the mMRC scale
| Grade | Description |
|---|---|
| 0 | Breathless only on strenuous exercise |
| 1 | Short of breath hurrying on the level, or walking up a slight hill |
| 2 | Walks slower than peers on the level, or stops for breath at own pace |
| 3 | Stops for breath after ~100 m or a few minutes on the level |
| 4 | Too breathless to leave the house, or breathless dressing or undressing |
Examination findings
| Sign | Mechanism |
|---|---|
| Barrel chest, reduced chest expansion | Chronic hyperinflation fixes the ribcage near full inspiration |
| Hyper-resonant percussion, loss of cardiac and hepatic dullness | Overinflated lung interposed over the heart and liver |
| Quiet breath sounds, prolonged expiratory phase | Reduced airflow; expiration takes longer than the normal 1:2 ratio |
| Expiratory wheeze | Turbulent flow through narrowed, collapsing airways |
| Pursed-lip breathing | Self-taught PEEP — back-pressure splints airways open and reduces trapping |
| Tripod posture, accessory muscle use | Fixing the shoulder girdle lets accessory muscles pull on the ribcage |
| Hoover's sign (inward costal margin movement on inspiration) | A flattened diaphragm pulls the lower ribs inward instead of outward |
| Central cyanosis | Significant hypoxaemia |
| Raised JVP, ankle oedema, tender hepatomegaly | Cor pulmonale — right heart failure from pulmonary hypertension |
| Asterixis, bounding pulse, drowsiness | CO₂ retention (hypercapnia) |
Finger clubbing is not a feature of COPD. If you find it in a COPD patient, you must actively look for something else — lung cancer (they share the same risk factor), bronchiectasis, or pulmonary fibrosis. The same applies to haemoptysis and to significant unexplained weight loss: neither is explained by COPD alone.
07Diagnosis & investigations
COPD is a physiological diagnosis confirmed by spirometry in a patient with appropriate symptoms and exposure. Everything else you order is to grade severity, find comorbidity, or exclude an alternative — not to make the diagnosis.
7.1 Spirometry — the mandatory test
Obstructive: FEV₁ ↓↓, FVC ↓ or normal, ratio ↓ (<0.70).
Air gets in but cannot get out.
Restrictive: FEV₁ ↓, FVC ↓↓, ratio normal or ↑ (≥0.70).
The lung cannot be filled in the first place.
The ratio is the discriminator — never the absolute FEV₁.
7.2 Imaging
The chest radiograph does not diagnose COPD, and can be normal in mild disease. Its job is to exclude the alternatives and detect complications. Compare the two films below.
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| Sign | Why it happens |
|---|---|
| Flattened hemidiaphragms | Trapped air pushes the diaphragm down and flattens its dome |
| More than 6 anterior / 10 posterior ribs visible | Lung fields extend abnormally far inferiorly |
| Hyperlucent lung fields, attenuated peripheral vessels | More air, and destroyed capillary bed |
| Narrow, vertical, "tubular" heart | Hyperinflated lungs compress and elongate the mediastinum |
| Increased retrosternal air space (>2.5 cm on lateral) | Anterior lung expansion behind the sternum |
| Bullae | Focal airspaces >1 cm from coalesced alveolar destruction |
7.3 Other investigations
| Test | Purpose | Typical finding in COPD |
|---|---|---|
| Pulse oximetry | Screen for hypoxaemia | SpO₂ may be reduced; cannot detect hypercapnia |
| Arterial blood gas | Mandatory if SpO₂ < 92%, or in any exacerbation | ↓PaO₂; ↑PaCO₂ with compensatory ↑HCO₃⁻ if chronic |
| Full blood count | Detect polycythaemia or anaemia | ↑Hb/haematocrit from chronic hypoxaemia |
| Blood eosinophil count | Guides whether to add an ICS | ≥300 cells/µL predicts good ICS response; <100 predicts poor |
| Alpha-1 antitrypsin level | Detect the genetic cause | Test once in every patient, especially if <45 y, non-smoker, or basal emphysema |
| ECG / echocardiogram | Assess the right heart | P pulmonale, right axis deviation, RV hypertrophy, RV dilatation |
| Sputum culture | Only in exacerbation with purulent sputum or treatment failure | H. influenzae, S. pneumoniae, M. catarrhalis; Pseudomonas in severe disease |
| Six-minute walk test | Functional capacity; feeds the BODE index | Reduced distance; may reveal exertional desaturation |
7.4 Differential diagnosis
| Condition | Discriminating features |
|---|---|
| Asthma | Onset in childhood; symptoms variable day to day and at night; atopy/eczema; largely reversible obstruction (FEV₁ ↑>12% and >200 mL); eosinophilic |
| Heart failure | Orthopnoea and paroxysmal nocturnal dyspnoea; fine basal crackles; cardiomegaly and pulmonary oedema on X-ray; raised BNP; restrictive not obstructive spirometry |
| Bronchiectasis | Very large sputum volumes; recurrent infection; clubbing; coarse crackles; tram-track and signet-ring signs on CT |
| Pulmonary tuberculosis | Fever, night sweats, weight loss, haemoptysis; upper-zone infiltrate or cavity; endemic exposure |
| Interstitial lung disease | Fine end-inspiratory crackles; clubbing; restrictive spirometry with ↓DLCO; reticular pattern on HRCT |
| Lung cancer | Haemoptysis, focal signs, marked weight loss, mass on imaging — and it frequently coexists with COPD |
| Anaemia / deconditioning / obesity | Normal spirometry; breathlessness without airflow obstruction |
08Management
Be honest about what treatment does. Inhalers relieve symptoms and reduce exacerbations, but the interventions with proven mortality benefit in COPD are: smoking cessation, long-term oxygen therapy in chronic severe hypoxaemia, and lung volume reduction surgery in carefully selected patients. Vaccination and pulmonary rehabilitation reduce admissions and transform quality of life. That hierarchy should shape every consultation.
8.1 Non-pharmacological management
| Intervention | Evidence / effect | Practical detail |
|---|---|---|
| Smoking cessation | The only intervention that slows FEV₁ decline. Reduces mortality | Combine behavioural support with pharmacotherapy (NRT, varenicline, bupropion). Ask and offer at every visit |
| Reduce biomass exposure | Improves symptoms; reduces progression | Ventilated stoves, chimneys, cleaner fuel — the key intervention in low-resource settings |
| Pulmonary rehabilitation | Improves exercise capacity, dyspnoea and quality of life more than any drug. Reduces readmission after exacerbation | 6–12 weeks of supervised exercise plus education. Refer anyone with mMRC ≥ 2, and after every hospitalisation |
| Vaccination | Reduces exacerbations, admissions and death | Annual influenza; pneumococcal; COVID-19; RSV and pertussis-containing boosters per local schedule |
| Nutritional support | Cachexia independently predicts mortality | Screen BMI; supplement if underweight; combine with resistance exercise |
| Inhaler technique review | Up to two-thirds of patients use devices incorrectly | Check technique at every review. A spacer improves MDI delivery substantially |
| Self-management & action plan | Earlier exacerbation treatment; fewer admissions | Written plan; recognise warning signs; when to start rescue therapy and when to seek help |
| Treat comorbidities | Cardiovascular disease often kills before the COPD does | Actively manage hypertension, ischaemic heart disease, osteoporosis, depression, anxiety, GORD |
8.2 Stepwise pharmacological approach (stable COPD)
Everyone gets a reliever
A short-acting bronchodilator (SABA and/or SAMA) as required, for immediate relief — at every stage of disease.
Group A — one long-acting bronchodilator
Low symptoms, no significant exacerbations. Start a LAMA or LABA; continue only if it demonstrably helps.
Groups B and E — dual bronchodilation
LABA + LAMA is now first-line for both high-symptom and exacerbating patients. Dual bronchodilation beats either agent alone for lung function, symptoms and exacerbations.
Escalate to triple therapy — but only on the biomarker
If exacerbations continue on LABA+LAMA, add an ICS (making LABA+LAMA+ICS) when blood eosinophils are ≥ 300 cells/µL, or ≥ 100 with frequent/severe exacerbations, or where there is concomitant asthma. Triple therapy reduces exacerbations and, in the IMPACT and ETHOS trials, mortality.
Still exacerbating — add-on options
Consider roflumilast if FEV₁ < 50% with chronic bronchitis, or long-term azithromycin (weigh QT prolongation, ototoxicity and resistance). Screen for and treat bronchiectasis and untreated comorbidity before adding more drugs.
Advanced disease — non-drug therapies
LTOT for chronic severe hypoxaemia; domiciliary NIV for persistent hypercapnia; lung volume reduction (surgical or endobronchial valves) in selected upper-lobe emphysema; transplantation in the very selected; and early, honest palliative care for refractory breathlessness.
In asthma, inhaled corticosteroids are foundational and used early. In COPD they are targeted: they help the eosinophilic minority and raise the risk of pneumonia, oral candidiasis, dysphonia and (with long-term high dose) osteoporosis. Prescribing ICS to a COPD patient with eosinophils <100 cells/µL is mostly risk with little benefit — check the count, then decide.
8.3 Managing an acute exacerbation
An exacerbation is an acute worsening beyond normal variation that requires a change in treatment. Confirm it is genuinely an exacerbation — pneumonia, pulmonary embolism, pneumothorax, heart failure and arrhythmia all masquerade as one.
| Step | Action | Detail |
|---|---|---|
| Controlled oxygen | Target SpO₂ 88–92% | Use a 24–28% Venturi mask. Titrate to the target and recheck the gas. Uncontrolled high-flow O₂ can worsen hypercapnia |
| Bronchodilators | Nebulised salbutamol + ipratropium | Drive the nebuliser with air, not oxygen, in a CO₂ retainer; give supplemental O₂ by nasal cannula alongside |
| Systemic corticosteroid | Prednisolone 40 mg PO daily for 5 days | Shortens recovery and reduces relapse. No taper needed for a short course; no benefit from longer courses |
| Antibiotics | Only if increased sputum purulence, or mechanical ventilation needed | Amoxicillin, doxycycline or a macrolide for 5 days per local resistance patterns. Purulence — not simply "more breathless" — is the trigger |
| Non-invasive ventilation | For persistent respiratory acidosis | pH < 7.35 with PaCO₂ > 6.5 kPa despite optimal therapy. NIV reduces intubation and mortality — do not delay it |
| Supportive care | VTE prophylaxis, fluids, treat comorbidity | Review before discharge: inhaler technique, action plan, rehab referral, smoking cessation, follow-up within 4 weeks |
Why target 88–92% rather than 94–98%? In a chronic CO₂ retainer, excess oxygen worsens hypercapnia mainly by releasing hypoxic pulmonary vasoconstriction — which increases perfusion to poorly ventilated lung and so worsens V/Q matching for CO₂ clearance — plus the Haldane effect, with a smaller contribution from reduced hypoxic ventilatory drive. But note the real priority: hypoxia kills faster than hypercapnia. Never withhold oxygen from a hypoxic patient. Give it in a controlled dose, and recheck the gas.
09Pharmacology
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9.1 Bronchodilators — the two mechanisms
Airway smooth muscle tone is set by a balance: sympathetic β₂ stimulation relaxes it, parasympathetic (vagal) M₃ stimulation contracts it. There are therefore exactly two ways to open an airway pharmacologically — push the relaxing pathway (β₂ agonists) or block the contracting pathway (muscarinic antagonists). That is why the two classes are additive, and why LABA+LAMA outperforms doubling either one.
| Class | Examples | Mechanism | Onset / duration | Key adverse effects |
|---|---|---|---|---|
| SABA | Salbutamol (albuterol), terbutaline | β₂ agonism → ↑cAMP → smooth muscle relaxation | ~5 min / 4–6 h | Tremor, tachycardia, palpitations, hypokalaemia, lactic acidosis at high dose |
| LABA | Formoterol, salmeterol, indacaterol, olodaterol, vilanterol | Same, with lipophilic anchoring for prolonged action | Formoterol fast; salmeterol slow / 12–24 h | As SABA; do not use as sole therapy in coexisting asthma |
| Class | Examples | Mechanism | Duration | Key adverse effects |
|---|---|---|---|---|
| SAMA | Ipratropium | Non-selective muscarinic blockade → abolishes vagal bronchoconstriction and mucus secretion | 6–8 h | Dry mouth, bitter taste; caution in narrow-angle glaucoma (nebulised mist) |
| LAMA | Tiotropium, glycopyrronium, umeclidinium, aclidinium | Prolonged M₃ blockade with faster dissociation from M₂ (kinetic selectivity) | 12–24 h | Dry mouth, constipation, urinary retention (caution in prostatism), blurred vision |
| Drug / class | Mechanism | Place in therapy | Cautions |
|---|---|---|---|
| ICS budesonide, fluticasone, beclometasone | Bind glucocorticoid receptors; suppress inflammatory gene transcription | Only as add-on to dual bronchodilation in exacerbators, guided by eosinophils (≥300, or ≥100 with frequent exacerbations) or coexisting asthma | ↑Pneumonia risk, oral candidiasis, dysphonia, easy bruising, osteoporosis at high cumulative dose. Rinse mouth after use |
| Systemic corticosteroid | As above, systemically | Acute exacerbation: 40 mg prednisolone daily × 5 days | Hyperglycaemia, insomnia, mood change, delirium; myopathy and adrenal suppression with repeated courses |
| Roflumilast | Selective PDE-4 inhibition → ↑cAMP in inflammatory cells → damps neutrophilic inflammation | Add-on in severe COPD (FEV₁ <50%) with chronic bronchitis and continued exacerbations | Diarrhoea, nausea, weight loss, headache, mood disturbance including suicidality. Avoid if underweight or depressed |
| Azithromycin (long-term) | Antibacterial plus immunomodulatory effects | Selected frequent exacerbators, ideally ex-smokers | QT prolongation, hearing loss, and driving macrolide resistance. Baseline ECG and exclude NTM first |
| Theophylline | Non-selective PDE inhibition and adenosine antagonism | Later-line only, where inhaled therapy is unavailable or insufficient | Narrow therapeutic index — arrhythmia, seizures, vomiting. Many CYP1A2 interactions (macrolides, ciprofloxacin, smoking status). Monitor levels |
| Mucolytics carbocisteine, N-acetylcysteine | Reduce sputum viscosity; NAC also antioxidant | Chronic productive cough; modest exacerbation reduction | Generally well tolerated; GI upset |
| Alpha-1 antitrypsin augmentation | Weekly IV infusion of pooled human A1AT restores antiprotease cover | Only in proven severe alpha-1 antitrypsin deficiency with emphysema | Costly, lifelong, specialist-initiated. No role in ordinary smoking-related COPD |
The doses quoted here are typical adult examples for teaching. Actual prescribing must follow your national formulary and local guideline, adjusted for renal and hepatic function, age, comorbidity and interactions. Never prescribe from a web article.
9.2 What the drugs do — and do not do
| Outcome | Bronchodilators | ICS (targeted) | Smoking cessation | Pulmonary rehab |
|---|---|---|---|---|
| Symptoms / dyspnoea | Improves | Modest | Improves | Improves most |
| Exacerbation frequency | Reduces | Reduces (if eosinophilic) | Reduces | Reduces readmission |
| Rate of FEV₁ decline | No | No | Yes — the only one | No |
| Mortality | No | Triple therapy: signal in IMPACT/ETHOS | Yes | Reduces post-exacerbation mortality |
10Complications & prognosis
| Complication | Mechanism | Clues |
|---|---|---|
| Acute exacerbation | Inflammatory flare, usually viral or bacterial | ↑Dyspnoea, ↑sputum volume/purulence beyond normal variation |
| Respiratory failure | Ventilatory load exceeds capacity | Type 2: ↓PaO₂ with ↑PaCO₂; drowsiness, asterixis, headache |
| Pulmonary hypertension | Hypoxic vasoconstriction, remodelling, capillary destruction | Loud P₂, RV heave; confirmed on echocardiogram |
| Cor pulmonale | Chronic RV pressure overload → RV failure | Raised JVP, ankle oedema, tender hepatomegaly |
| Pneumothorax | Rupture of a subpleural bulla | Sudden pleuritic pain and disproportionate dyspnoea. Poorly tolerated — little reserve |
| Secondary polycythaemia | Erythropoietin response to chronic hypoxaemia | ↑Hb and haematocrit; hyperviscosity raises thrombotic risk |
| Lung cancer | Shared risk factor plus chronic inflammation. COPD is an independent risk factor | New haemoptysis, weight loss, clubbing, or a new mass/nodule |
| Cardiovascular disease | Shared risk factors plus systemic inflammation | Often the actual cause of death in mild–moderate COPD |
| Osteoporosis | Inactivity, steroids, smoking, low BMI, systemic inflammation | Fragility fracture; vertebral fracture worsens restriction |
| Depression & anxiety | Breathlessness, isolation, loss of function | Grossly underdiagnosed — screen for it deliberately |
| Skeletal muscle dysfunction / cachexia | Deconditioning plus systemic inflammatory catabolism | Quadriceps wasting; independently predicts mortality |
Prognosis — the BODE index
FEV₁ alone is a mediocre predictor of death. The BODE index performs substantially better by adding body composition, symptoms and exercise capacity — a reminder that COPD is a systemic disease, not merely a spirometry number.
| Variable | 0 pts | 1 pt | 2 pts | 3 pts |
|---|---|---|---|---|
| B — Body mass index | > 21 | ≤ 21 | — | — |
| O — Obstruction (FEV₁ % pred) | ≥ 65 | 50–64 | 36–49 | ≤ 35 |
| D — Dyspnoea (mMRC) | 0–1 | 2 | 3 | 4 |
| E — Exercise (6-min walk, m) | ≥ 350 | 250–349 | 150–249 | ≤ 149 |
Low FEV₁ and rapid decline; frequent exacerbations, especially those needing admission; chronic hypoxaemia or hypercapnia; pulmonary hypertension and cor pulmonale; low BMI and muscle wasting; reduced exercise capacity; continued smoking; and a heavy comorbidity burden. One severe exacerbation requiring admission carries roughly a 1-in-4 one-year mortality — comparable to many cancers, and a fact worth stating plainly when discussing prognosis and advance care planning.
You have read the theory. Now manage the patient.
A breathless smoker arrives with worsening dyspnoea and purulent sputum. You choose the oxygen target, the bronchodilators, whether to give steroids and antibiotics, and when to escalate to NIV — and a live physiology engine responds to every decision. Set the oxygen wrong and watch the CO₂ climb.
Open DoctriosKey references & further reading
- Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of COPD — 2024 Report. goldcopd.org
- World Health Organization. Chronic obstructive pulmonary disease (COPD) — fact sheet. who.int
- National Institute for Health and Care Excellence. NG115: COPD in over 16s — diagnosis and management. nice.org.uk
- Lipson DA et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD (IMPACT). N Engl J Med 2018;378:1671–80.
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Educational content only. This article is written for medical students, interns and qualified clinicians as a study and revision resource. It is not medical advice, not a diagnostic tool, and not a substitute for professional clinical judgement or your local guideline and formulary. If you have symptoms, consult a qualified clinician. Doses stated are illustrative teaching examples only.